Ethyl Acetoacetate → Ethyl 2-bromo-6-methyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylate

HRID 1642069Notes

Reaction equation

[H-].[Na+].[C:3]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:4][C:5]([CH3:7])=O.Br[C:13]1[C:14]([NH2:20])=[N:15][CH:16]=[C:17]([Br:19])[N:18]=1>CN1CCCC1>[CH2:10]([O:9][C:3]([C:4]1[C:13]2[C:14](=[N:15][CH:16]=[C:17]([Br:19])[N:18]=2)[NH:20][C:5]=1[CH3:7])=[O:8])[CH3:11]

Participants

Conditions

Temperature: 140 °C

Procedure

To a flask charged with 20 mL of anhydrous N-methylpyrrolidine at 0° C. was added 60% NaH (840 mg, 21 mmol). After stirring 15 min, ethyl acetoacetate (2.73 g, 10.8 mmol) was added slowly. After stirring an additional 20 min 3,5-Dibromo-pyrazin-2-ylamine (5.04 g, 20 mmol). The reaction vessel was then removed from the ice bath and heated to 140° C. for 3 days. The dark mixture was cooled to rt and diluted with diethyl ether and water. The mixture was filtered and then partitioned. The organic layer was washed with water and then brine, dried over Na2SO4, filtered, and concentrated to afford a dark red oil. This was purified by silica gel chromatography (4:1 Hexanes:EtOAc) to afford 290 mg of 2-Bromo-6-methyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ethyl ester.

Workup

customThe reaction vessel was then removed from the ice bath
temperatureThe dark mixture was cooled to rt
additiondiluted with diethyl ether and water
filtrationThe mixture was filtered
custompartitioned
washThe organic layer was washed with water
dry with materialbrine, dried over Na2SO4
filtrationfiltered
concentrationconcentrated
customto afford a dark red oil
customThis was purified by silica gel chromatography (4:1 Hexanes:EtOAc)

Sources & evidence

ORD record: ord-64b8da95d29f4489815f223faf6934ba
Source dataset: uspto-grants-2012_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08119636B2

Reaction notes

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